Optimisation and assessment of airway clearance in children with cystic fibrosis

Abstract

Cystic Fibrosis (CF) is the most common life-shortening genetic disorder in the white population.1 It affects approximately 1300 individuals in the Netherlands2 and 60.000 individuals worldwide. CF is caused by mutations in the cystic fi brosis transmembrane conductance regulator (CFTR) gene, which is expressed in many organ systems, including the respiratory and gastro-intestinal tracts. Over 1600 mutations of the CFTR gene have been described. The prevalent mutation leading to CF is the deletion of phenylalanine at codon 508 (phe508del, until recently known as ΔF508). This is found in about 70% of the patients. Different mutations in the CFTR gene have varying effects on CFTR function and can result in different phenotypes of the disease. The CFTR protein primarily functions as an ion channel that regulates liquid volume on epithelial surfaces through chloride secretion and inhibition of sodium absorption. Impaired or absent CFTR function leads to a reduced volume of airway surface liquid in the lungs, which negatively affects the mucociliary clearance (MCC). This in turn leads to chronic and severe lung disease that starts in infancy. Treatment of CF is lifelong, complex and intensive. Fortunately, the predicted survival of CF patients has steadily improved over the last decades. The median age of survival in the United States reached 36.9 years in 2006.3 This progress is due to much better nutritional management, the provision of care through multidisciplinary specialized CF centres, and more effective antibiotics and mucolytic agents.